Welcome! Thank you for joining the American College of Physicians’ Quality Connect Adult Immunization Learning Series Webinar! We will start in a few minutes. Today’s webinar is focused on influenza, vaccinating patients 65+, and clarification on the LAIV change. Please keep your phone on mute, when not asking questions, we are recording this webinar. Feel free to ask questions in the chat feature of WebEx. ACP will share the slides and recorded webinar on MedConcert.

Today’s Speaker William Schaffner, MD, MACP Professor of Preventive Medicine and Infectious Diseases Vanderbilt University Medical Center

Webinar Overview Focused on the 2016 – 2017 influenza season Learn tips on reaching your 65+ year old patients and what vaccines to use Understand and learn information on the LAIV vaccine change

Preventing Influenza – Reaching Your Patients 65+ and Feeling Confident for the Upcoming 2016-2016 season William Schaffner, MD August 9, 2016 Adult Immunization Learning Series Webinar

Potential Conflicts of Interest Merck: Member, Data Safety Monitoring Board Pfizer: Member, Data Safety Monitoring Board Dynavax: Consultant Novavax: Consultant Genentech: Lecture

AGENDA Influenza background Influenza vaccines, 2016 Influenza vaccines for persons age 65+ Why recommendation not to use nasal spray vaccine What about egg allergy?

INFLUENZA – BURDEN OF DISEASE

Variability in Season Onset Percentage of Visits for Influenza-like Illness (ILI) Reported to CDC ILINet For Selected Previous Seasons from all US States CDC. FluView Interactive. http://gis.cdc.gov/GRASP/Fluview

Influenza Virus Surveillance 2011-2015 US Public Health Laboratories A(H3N2) A(H1N1) pandemic B/Yam & B/Vic 2014 2013 2012

Annual Influenza Impact Varies by Season Reed et al. PLOS One 10(3):e0118369 http://www.cdc.gov/flu/about/disease/2014-15.htm

Annual Influenza Impact Varies by Age Group 2010-11 2011-12 2012-13 2013-14 2014-15 Cases Hospitalizations Reed et al. PLOS One 10(3):e0118369 Foppa et al. Vaccine 33 (2015) 3003–3009

Annual Influenza Impact by Age Group 2010-11 2011-12 2012-13 2013-14 2014-15 Cases Hospitalizations 2014-15 H3N2 Drift Season: 974,206 Hospitalizations 40,435,474 Cases Reed et al. PLOS One 10(3):e0118369 http://www.cdc.gov/flu/about/disease/2014-15.htm

INFLUENZA VACCINE

INFLUENZA VACCINES VACCINE COMMENT Trivalent IM Intradermal Recombinant Standard Age 18 - 64 No egg High Dose 65+ Adjuvant Quadrivalent IM Cell culture LAIV Added B strain Minimal egg Do not use this season

VACCINE Effectiveness Our patients (and we) want: Side effects = 0 Effectiveness = 100% Effectiveness varies by year, age, underlying illness, each viral strain Age 15 - 64 62 - 76% Age 65+ 26 - 52% Prevention: hospitalization, ICU, death transmission to others

Influenza Deaths Averted Foppa et al. Vaccine 33 (2015) 3003–3009

Number Needed to Vaccinate Number Needed to Vaccinate to Prevent One Influenza Hospitalization or Case with Increasing Vaccine Effectiveness, US 2014-15 Influenza Season Number Vaccinated Biggerstaff et al. CDC unpublished data. 2016

Recommendation for Vaccinating 65+ First Influenza Vaccine Recommendation By Surgeon General Burney in: Public Health Rep. 1960 Oct;75(10):944.

Percent of Population 65+ Projected Administration on Aging. http://www.aoa.acl.gov/Aging_Statistics/future_growth/future_growth.aspx#age

High-Dose Influenza Vaccine (Fluzone-HD, Sanofi-Pasteur) 4X the HA content (60 mcg) of standard vaccine (15 mcg) of each strain Trivalent During 2015 - 16 season, about 50% of immunized seniors

High-Dose Influenza Vaccine Post-licensure Efficacy Trial Relative efficacy vs standard Overall + 24.2% Age 65 - 74 + 19.7% 75+ + 32.0% Hospitalization (all cause) + 6.9% Serious cardio-resp events + 17.7% Pneumonia (30 days) + 39.8% CHF + 24.0% Cerebrovascular events + 6.5%

High-Dose Influenza Vaccine Post-licensure Efficacy Trial Relative efficacy vs standard No frailty condition 34% 1 frailty condition 27.5% 2 frailty conditions 23.9% 3+ frailty conditions 16%

Adjuvanted Influenza Vaccine (Fluad, Seqirus) Oil-in-water adjuvant (MF59) Squalene – biodegradable intermediate precursor cholesterol biosynthetic pathway Worldwide - licensed in 30+ countries 100 million+ doses

Adjuvanted Influenza Vaccine Relative immunogenicity Adjuvanted vs standard vaccine (16 RCT) Viral strain H1N1 + 9.5% H3N2 + 10.5% B + 12.7%

Adjuvanted Influenza Vaccine Open, comparative, observational study (Italy) 25% reduction in hospitalizations Prospective, community, case-control (Canada) Overall enhanced effectiveness: 35%

Decision Not to Recommend the Use of Live, Attenuated Nasal Spray Influenza Vaccine this Season

US Flu VE Network, Ages 2-17 Any influenza A or B 2010-11 Mixed 2011-12 H3N2 2012-13 2013-14 H1N1 2014-15 2015-16 LAIV 71 67 46 -1 3 IIV 55 45 60 15 63 LAIV 3 LAIV 4 IIV3 IIV 3/4

2015-2016: Summary of US Data US Flu VE: No LAIV effectiveness vs H1N1 DOD: No LAIV effectiveness vs H1N1 AstraZeneca: LAIV effectiveness vs H1N1 not significant Significant VE for IIV All studies reported higher VE for IIV than LAIV

Hypotheses Suboptimal performance of the H1N1 component Possible interference among viruses in quadrivalent vaccine Reduced immunogenicity of LAIV because children now more highly vaccinated

ACIP VOTE For the 2016-2017 influenza vaccination season, LAIV is not recommended.

EGG ALLERGY Numerous studies (over 5,000 pts) US and European Allergy Societies “Egg allergy does NOT impart increased risk of anaphylactic reaction to immunization with either IIV or LAIV”

EGG ALLERGY Eats eggs OK HIVES often after eggs Severe reaction after eggs Previous severe reaction to vaccine Vaccinate as usual RIV or Vaccinate as usual and observe for 30 minutes vaccinate as usual and observe for 30 minutes; experienced physician Contraindication to vaccine

Discussion and Questions Contact Information William.Schaffner@Vanderbilt.edu